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Natural Products Lysobactin and Sorangicin A Show In Vitro Activity against Mycobacterium abscessus Complex

The prevalence of lung disease caused by Mycobacterium abscessus is increasing among patients with cystic fibrosis. M. abscessus is a multidrug resistant opportunistic pathogen that is notoriously difficult to treat due to a lack of efficacious therapeutic regimens. Currently, there are no standard...

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Autores principales: Sullivan, Jaryd R., Yao, Jacqueline, Courtine, Christophe, Lupien, Andréanne, Herrmann, Jennifer, Müller, Rolf, Behr, Marcel A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Microbiology 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9769517/
https://www.ncbi.nlm.nih.gov/pubmed/36342177
http://dx.doi.org/10.1128/spectrum.02672-22
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author Sullivan, Jaryd R.
Yao, Jacqueline
Courtine, Christophe
Lupien, Andréanne
Herrmann, Jennifer
Müller, Rolf
Behr, Marcel A.
author_facet Sullivan, Jaryd R.
Yao, Jacqueline
Courtine, Christophe
Lupien, Andréanne
Herrmann, Jennifer
Müller, Rolf
Behr, Marcel A.
author_sort Sullivan, Jaryd R.
collection PubMed
description The prevalence of lung disease caused by Mycobacterium abscessus is increasing among patients with cystic fibrosis. M. abscessus is a multidrug resistant opportunistic pathogen that is notoriously difficult to treat due to a lack of efficacious therapeutic regimens. Currently, there are no standard regimens, and treatment guidelines are based empirically on drug susceptibility testing. Thus, novel antibiotics are required. Natural products represent a vast pool of biologically active compounds that have a history of being a good source of antibiotics. Here, we screened a library of 517 natural products purified from fermentations of various bacteria, fungi, and plants against M. abscessus ATCC 19977. Lysobactin and sorangicin A were active against the M. abscessus complex and drug resistant clinical isolates. These natural products merit further consideration to be included in the M. abscessus drug pipeline. IMPORTANCE The many thousands of people living with cystic fibrosis are at a greater risk of developing a chronic lung infection caused by Mycobacterium abscessus. Since M. abscessus is clinically resistant to most anti-TB drugs available, treatment options are limited to macrolides. Despite macrolide-based therapies, cure rates for M. abscessus lung infections are 50%. Using an in-house library of curated natural products, we identified lysobactin and sorangicin A as novel scaffolds for the future development of antimicrobials for patients with M. abscessus infections.
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spelling pubmed-97695172022-12-22 Natural Products Lysobactin and Sorangicin A Show In Vitro Activity against Mycobacterium abscessus Complex Sullivan, Jaryd R. Yao, Jacqueline Courtine, Christophe Lupien, Andréanne Herrmann, Jennifer Müller, Rolf Behr, Marcel A. Microbiol Spectr Research Article The prevalence of lung disease caused by Mycobacterium abscessus is increasing among patients with cystic fibrosis. M. abscessus is a multidrug resistant opportunistic pathogen that is notoriously difficult to treat due to a lack of efficacious therapeutic regimens. Currently, there are no standard regimens, and treatment guidelines are based empirically on drug susceptibility testing. Thus, novel antibiotics are required. Natural products represent a vast pool of biologically active compounds that have a history of being a good source of antibiotics. Here, we screened a library of 517 natural products purified from fermentations of various bacteria, fungi, and plants against M. abscessus ATCC 19977. Lysobactin and sorangicin A were active against the M. abscessus complex and drug resistant clinical isolates. These natural products merit further consideration to be included in the M. abscessus drug pipeline. IMPORTANCE The many thousands of people living with cystic fibrosis are at a greater risk of developing a chronic lung infection caused by Mycobacterium abscessus. Since M. abscessus is clinically resistant to most anti-TB drugs available, treatment options are limited to macrolides. Despite macrolide-based therapies, cure rates for M. abscessus lung infections are 50%. Using an in-house library of curated natural products, we identified lysobactin and sorangicin A as novel scaffolds for the future development of antimicrobials for patients with M. abscessus infections. American Society for Microbiology 2022-10-31 /pmc/articles/PMC9769517/ /pubmed/36342177 http://dx.doi.org/10.1128/spectrum.02672-22 Text en Copyright © 2022 Sullivan et al. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Article
Sullivan, Jaryd R.
Yao, Jacqueline
Courtine, Christophe
Lupien, Andréanne
Herrmann, Jennifer
Müller, Rolf
Behr, Marcel A.
Natural Products Lysobactin and Sorangicin A Show In Vitro Activity against Mycobacterium abscessus Complex
title Natural Products Lysobactin and Sorangicin A Show In Vitro Activity against Mycobacterium abscessus Complex
title_full Natural Products Lysobactin and Sorangicin A Show In Vitro Activity against Mycobacterium abscessus Complex
title_fullStr Natural Products Lysobactin and Sorangicin A Show In Vitro Activity against Mycobacterium abscessus Complex
title_full_unstemmed Natural Products Lysobactin and Sorangicin A Show In Vitro Activity against Mycobacterium abscessus Complex
title_short Natural Products Lysobactin and Sorangicin A Show In Vitro Activity against Mycobacterium abscessus Complex
title_sort natural products lysobactin and sorangicin a show in vitro activity against mycobacterium abscessus complex
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9769517/
https://www.ncbi.nlm.nih.gov/pubmed/36342177
http://dx.doi.org/10.1128/spectrum.02672-22
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